The major purpose of the Neuropathology Core (NP Core) is to perform diagnostic neuropathologic evaluations on brains of participants in the Einstein Aging Study (EAS). To accomplish this aim, the NP Core integrates its activities with the Einstein/Montefiore Pathology Departmental on-call service for harvesting brains of subjects enrolled in the EAS in a timely fashion and according to protocol. The NP Core uses standardized dissection and processing procedures and collects neuropathologic data from all brains with the following methods: a. Gross examination with digital photography, b. Assessment of histopathology, c. Lesion counts with thioflavin-S fluorescent microscopy, and d. PHF-tau immunostained sections for staging Alzheimer type pathology. For cases with vascular lesions, gross lesions are photographed and the number, type and distribution of lesions are documented. In cases with either neuronal loss or Lewy bodies in the substantia nigra, multiple sections are immunostained with antibodies to synuclein. The amygdala of all AD cases is screened for synuclein immunoreactive Lewy bodies and for 4-repeat tau immunoreactive argyrophilic grains. When detected, the density of Lewy bodies is determined in multiple cortical areas and the amygdala. Non-Alzheimer degenerative dementias are characterized with immunocytochemistry and antibodies to neurofilament, ubiquitin and PHF-tau. Microglial immunohistochemistry is also routinely used to demonstrate diverse pathologies. The NP Core provides fixed and frozen brain samples to Project 3 for immunocytochemical, image analytical and enzyme linked immunosorbent assays. Tissue is provided to other qualified investigators with approval of the Administrative Core. The NP Core determines apolipoprotein-E genotypes and TAU haplotypes and banks DNA and RNA from brain tissue. Tissue quality is also assessed with pH and western blots for HSP70. Tissue samples, slides and paraffin blocks are banked for future studies. Reports are provided to the Administrative Core and data to the Statistical Core using standardized protocols and procedures.